中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (10): 1803-1807.doi: 10.3969/j.issn.1673-8225.2010.10.019

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

神经干细胞移植对阿尔茨海默病大鼠海马突触素表达和学习记忆能力的影响

杨 春1,周 辉2,白琳琳3,王书春1,章 茜1   

  1. 郑州大学,1基础医学院生理学教研室,2第一附属医院神经外科,河南省郑州市  450052;
    3濮阳市卫生局,河南省濮阳市  457000
  • 出版日期:2010-03-05 发布日期:2010-03-05
  • 通讯作者: 章 茜,博士,教授,郑州大学基础医学院生理学教研室,河南省郑州市 450052 qianzhang@ zzu.edu.cn
  • 作者简介:杨 春,女,1975年生,辽宁省海城市人,汉族,2004年郑州大学毕业,硕士,讲师,主要从事神经生理学的研究。 yangchun@zzu.edu.cn
  • 基金资助:

    河南省医学创新人才基金资助项目(2002115)

Effects of neural stem cell transplantation on hippocampus synaptophysin expression and learning memory abilities of Alzheimer disease rats

Yang Chun1, Zhou Hui 2, Bai Lin-lin3, Wang Shu-chun1, Zhang Qian1   

  1. 1Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou  450052, Henan Province, China;
    2Department of Neurosurgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou  450052, Henan Province, China
  • Online:2010-03-05 Published:2010-03-05
  • Contact: Zhang Qian, Doctor, Professor, Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou 450052, Henan Province, China qianzhang@zzu. edu.cn
  • About author:Yang Chun, Master, Lecturer, Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou 450052, Henan Province, China yangchun@zzu.edu. cn
  • Supported by:

    the Innovation Talent Program in Medical Science and Technology of Henan Province, No. 2002115*

摘要:

背景:前期实验已证实,移植入阿尔茨海默病大鼠脑内的神经干细胞能够存活、增殖,但其是否可替代损伤或坏死的神经细胞而重建神经通路,改善学习记忆能力尚不清楚。突触素是突触重建的重要标记之一。

目的:观察神经干细胞移植对阿尔茨海默病大鼠学习记忆能力及突触表达的影响。

方法:SD大鼠随机数字表法分为正常对照组、阿尔茨海默病模型组、2周移植组和4周移植组,除正常对照组外制备阿尔茨海默病模型。另取新生24 h SD大鼠海马齿状回分离、培养神经干细胞,经Hoechst33258标记后植入2周和4周移植组海马CA1区,行Y迷宫实验检测大鼠的学习记忆能力,然后取脑进行尼氏染色和突触素免疫组织化学染色。阿尔茨海默病模型组则以同样的方法、同样的位点注入等量无菌生理盐水。正常对照组不施以任何处理。

结果与结论: ①2周和4周移植组海马CA1区细胞比阿尔茨海默病模型组增多,但仍少于正常对照组(P < 0.05),平均吸光度与正常对照组相比差异无显著性意义(P > 0.05)。②2周移植组和4周移植组大鼠海马结构内突触素吸光度值明显高于正常对照组和阿尔茨海默病模型组(P < 0.05)。③与阿尔茨海默病模型组相比,2周和4周移植组大鼠学习能力和记忆能力均显著增强,正确反应率明显提高(P < 0.05),而与正常对照组相比,差异无显著性意义(P > 0.05)。提示移植入脑内的神经干细胞可促进突触形成,改善学习记忆能力。

关键词: 神经干细胞, 阿尔茨海默病, 突触素, 海马, 学习记忆

Abstract:

BACKGROUND: Previous studies have demonstrated that transplanted neural stem cells can survive and proliferate in the brain of Alzheimer disease (AD) rats, however, it is poorly understood whether it can rebuild the nerve tracts by substituting the injured or dead neurons and improve learning and memory abilities. Synaptophysin is one of the important markers of synaptic rebuilding.

OBJECTIVE: To observe the effects of neural stem cell transplantation on synaptophysin expression in hippocampus and learning and memory abilities of AD rats.

METHODS: Sprague Dawley rats were randomly divided into the normal control, AD model, 2-week-transplantation and 4-week-transplantation groups. All rats were established AD models except that in the normal control group. Neural stem cells were isolated from the dentate gyrus of hippocampus of newborn rats, labeled with Hoechst33258, and then transplanted into CA1 region of hippocampus of rats in the 2-week-transplantation and 4-week-transplantation groups. The behavioral testing in the rats was performed using Y-maze trial. Nissl staining and synaptophysin immunohistochemistry were detected after the rats were sacrificed. The same volume of stroke-physiological saline solution was injected into rats in the AD models group using the identical methods. There was no treatment in the normal control group.

RESULTS AND CONCLUSION: ①The cells number in the hippocampal CA1 region of the 2-week-transplantation and 4-week-transplantation groups were increased than that of AD model group, but were still less than that of the normal control group (P < 0.05). There was no significantly difference between the absorbance values of 2- or 4- week-transplantation group and control group (P > 0.05). ②The absorbance values of the 2-week-transplantation and 4-week-transplantation were significantly greater than that of the control and AD model groups (P < 0.05). ③The learning and memory abilities in 2- and 4-week-transplantation group enhanced obviously and their correct reaction rates improved evidently, which was found statistically significant difference from AD model group (P < 0.05), while no statistically significant difference from control group (P > 0.05). The transplanted neural stem cells may promote the synaptic rebuilding and improve learning and memory abilities in AD rats.

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